METHODS: Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes.
RESULTS: Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality.
CONCLUSIONS: Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.
方法:在试验期间(中位5.5年),随访了8000名高血压参与者(4305名患者接受氨氯地平±培多普利治疗,4275名患者接受阿替洛尔±利尿剂治疗,随访时间长达21年(中位17.4年),使用关联的医院和死亡率记录。试验结束后6年,对一组参与者(n=2156)进行了自我问卷调查和临床访问。试验中平均SBP和访视SBP的标准偏差作为BPV的量度,使用>100000BP测量进行测量。Cox比例风险模型用于估计风险[风险比(HR)],与(I)试验期间SBP和BPV的平均值相关,对于在试验结束后发生的CV终点和(ii)随机分配治疗随机分组后的事件,首次出现预先指定的CV结果。
结果:使用试用期的BP数据,在审判后阶段,尽管平均SBP是CV结果的预测因子{HR每10mmHg,1.14[95%置信区间(CI)1.10-1.17],P<.001},独立于平均SBP的收缩期BPV是CV事件的强预测因子[HR/5mmHg1.22(95%CI1.18-1.26),P<.001]和预测事件,即使在血压控制良好的参与者中也是如此。在21年的随访中,与以阿替洛尔为基础的试验治疗相比,以氨氯地平为基础的患者卒中风险显著降低[HR0.82(95%CI0.72-0.93),P=.003],总CV事件[HR0.93(95%CI0.88-0.98),P=.008],总冠状动脉事件[HR0.92(95%CI0.86-0.99),P=.024],和心房颤动[HR0.91(95%CI0.83-0.99),P=.030],心血管死亡率差异的证据较弱[HR0.91(95%CI0.82-1.01),P=.073]。非致死性心肌梗死和致死性冠心病的发生率无显著差异,心力衰竭,和全因死亡率。
结论:收缩期BPV是CV结局的强预测因子,即使是那些控制SBP的人。与基于阿替洛尔的治疗相比,基于氨氯地平的治疗在减少CV事件方面的长期益处似乎主要由试验期间对收缩期BPV的影响介导。